POS0669 TAPERING SUBCUTANEOUS METHOTREXATE CAUSES MORE DISEASE FLARES COMPARED TO ORAL ADMINISTRATION IN ESTABLISHED RHEUMATOID ARTHRITIS PATIENTS.
Authors: A. Looijen, E. Van Mulligen, A. Van der Helm-van Mil, P. De Jong
Journal: Annals of the Rheumatic Diseases (2022)

Background Thanks to improved treatment strategies, disease remission in rheumatoid arthritis(RA) patients has become more common. Therefore, current guidelines recommend to consider tapering DMARDs, including methotrexate(MTX), in patients who are in sustained remission. Previous research has shown that subcutaneous methotrexate(MTXsc) has a better bioavailability, efficacy and tolerability in active RA than oral MTX[1]. However, these advantages might be a disadvantage when tapering of MTXsc is considered. Objectives To compare the 1-year cumulative flare rates between established RA patients who taper subcutaneous and oral MTX. Methods Data from the TApering strategies in Rheumatoid Arthritis(TARA) trial were used[2]. In this trial, established RA patients with a well-controlled disease, defined as Disease Activity Score(DAS)≤2.4 and swollen joint count(SJC)≤1, using ≥1 csDMARD and TNF-inhibitor(TNFi) were included. Participants were randomized into two groups which gradually tapered their csDMARD first followed by the TNFi, or vice versa. The csDMARD was tapered by reducing the dosage by a half at baseline, by a quarter at 3 months and was stopped at 6 months. Patients who tapered MTX were included in this analysis. If a disease flare(DAS&gt;2.4 or SJC&gt;1) occurred, the last effective therapy was restarted and intensified every 3 months, until DAS≤2.4 and SJC≤1. Following an intention-to-treat principle, flare rates were compared between patients who tapered subcutaneous and oral MTX, using a chi-square test. Two sensitivity analyses were performed were we 1) only included patients with a complete follow-up; and 2) assumed that patients developed a flare at the moment of drop-out. Results A total of 71 and 17 patients respectively used oral and subcutaneous MTX. The median disease duration was 5.9 years and 70% was female. The median MTX dosage for both administration routes was 20 milligrams per week. After 12 months, 53% of patients who tapered MTXsc developed a flare compared to 27% who tapered oral MTX (OR 3.1(1.0-9.1, 95%CI), p=0.037)(Figure 1). Respectively 68% and 67% of the patients who developed a flare and were using oral and subcutaneous MTX had a well-controlled disease 3 months after restarting their treatment(p=0.93). Both sensitivity analyses showed similar results. Figure 1. Flare development and resolution over time for different administration routes of methotrexate. The first part on the X-axis illustrates the cumulative % of patients that develop a disease flare during follow up, the second part illustrates the cumulative % of patients that still has active disease (DAS&gt;2.4 +/ SJC44&gt;1) from point of flare development and after restarting the last effective treatment. Abbreviations: DAS, Disease Activity Score; MTX, methotrexate; SJC44, swollen joint count measured in 44 joints. Conclusion Patients who tapered MTXsc have a higher chance at developing a disease flare compared to those who tapered oral MTX. This could be explained by a higher efficacy of MTXsc when similar dosages are used[1]. Alternatively, the better tolerability of MTXsc, especially regarding gastro-intestinal side effects[1], may lead to a difference in adherence. When deciding to taper MTX, the administration route should be taken into account. Because of the increased risk of flare after tapering MTXsc, these patients could be monitored more closely than those tapering oral MTX. References [1]Li D, Yang Z, Kang P, Xie X. Subcutaneous administration of methotrexate at high doses makes a better performance in the treatment of rheumatoid arthritis compared with oral administration of methotrexate: A systematic review and meta-analysis. Semin Arthritis Rheum. 2016 Jun; 45(6):656-662. [2]van Mulligen E, de Jong PHP, Kuijper TM, van der Ven M, Appels C, Bijkerk C, et al. Gradual tapering TNF inhibitors versus conventional synthetic DMARDs after achieving controlled disease in patients with rheumatoid arthritis: first-year results of the randomised controlled TARA study. Ann Rheum Dis. 2019 Jun; 78(6):746-753. Disclosure of Interests None declared